Hepatic arterial infusion of gemcitabine-oxaliplatin in a large metastasis from colon cancer

Hepatic arterial infusion (HAI) of chemotherapy can be performed in cases of liver-confined metastatic disease,resulting in increased local drug concentrations.Here we report the case of a 61-year-old man who presented with an isolated large unresectable liver metastasis of colon cancer after failure of surgery and multiple administration of systemic chemotherapy.The patient was treated with a combination of gemcitabine and oxaliplatin using HAI.The tolerance was excellent and a radiological complete response was obtained after 8 cycles of HAI.The rationale for the use of gemcitabine and oxaliplatin as well as that for the combination of the 2 drugs is discussed in this paper.HAI of gemcitabine-oxaliplatin should be evaluated in further clinical trials.

In vivo comparison of transduction efficiency with recombinant adenovirus-mediated p53 in a human colon cancer mouse model by different delivery routes

Objective： To evaluate transduction efficiency with recombinant adenovirus-mediated p53 （rAd/p53） therapy in a human colon cancer mouse model by intra-tumoral injection and intra-arterial delivery. Methods： The tumor pieces of human colon cancer SW480 were implanted in the livers of 45 nude mice. These mice were administrated with rAd/p53 by intratumoral injection and intra-artedal delivery. After 24 h, 48 h and 72 h tAd/p53 administration, 5 mice each group were killed with over anesthesia and their livers were removed. P53 expression and apoptosis of tumor and liver were assessed. Results： P53 expression and apoptosis of intratumoral administration group was higher than tail vein group and control group. Apoptosis and p53 expression of livers in three groups had no significant difference. Conclusion： p53 gene transducUon efficiency and anticancer effect of rAd/p53 is much better by intra-tumoral injection than intra-arterial delivery,

Target gene prediction and functional analysis of miRNAs differently expressed in colon cancer primary tumors to metastases formed in the liver

Background:Colon cancer is one of the main tumor-related causes of death worldwide and now surgical resection is still the most effective method for the treatment of colon cancer.However,many colon cancers currently lose the opportunity for surgical treatment because of liver metastases.The possible molecular mechanism of liver metastasis of colon cancer can provide ideas for the prevention and treatment of liver metastasis colon cancer.Several studies have recently indicated the regulatory effects of microRNAs(miRNAs)in cancer metastasis.Bioinformatics methods were used to analyze the differentially expressed miRNAs in primary colon cancer tissues and liver metastases.Then the target genes of differentially expressed miRNAs were predicted.By analyzing the biological processes and signaling pathways that the target gene may participate in,we infer the possible molecular mechanisms of liver metastasis of colon cancer and the effects of target genes on prognosis of patients were explored.Methods:The chip data GSE98406 was selected and differentially expressed miRNAs between primary colon cancer and liver metastatic colon cancer were explored by Morpheus.TargetScan and miRanda were used to predict target genes of differentially expressed miRNAs.The gene oncology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to analyze the biological processes and possible signaling pathways the target genes involved in.Protein-ptotein interaction analysis was performed by String and Cyotscape,the interactions among target genes and hub genes were analyzed.Finally,we explored the effects of differentially expressed miRNAs and their target genes on the prognosis of colon cancer patients.Results:Two differentially expressed miRNAs were screened out,of which miR-122 was upregulated more than 2 folds and miR-143 was downregulated more than twofold in liver metastatic colon cancer.Target genes of miR-122 and miR-143 were mainly involved in energy metabolism.The major signaling pathways involved are epithelial-mesenchymal transition pathways.Ten hub genes were selected by protein interaction analysis.Among them,KRAS,CDK1,CREB1,CS,PC,RAB7A,and CANX were highly expressed in tumor tissues,and CALM1 and MAPK7 were lowly expressed in tumor tissues.The results showed that reduced expression of CS and PC reduced survival of patients with colon cancer.However,the impact of miR-122 and mi-143 on the prognosis of patients with colon cancer is not clear.Conclusion:Differentially expressed miRNAs mainly affect the expression of target genes involved in energy metabolism and cellular transformation in colon cancer.Intracellular metabolic activity is the center of cellular activity,the treatment of metabolic processes in tumor cells may be a new idea for the treatment of tumors.

Retinoblastoma binding protein 4 up-regulation is correlated with hepatic metastasis and poor prognosis in colon cancer patients

Background: Retinoblastoma binding protein 4 (RBBP4) plays an essential role in the development of multiple cancers. However, its relationship with prognosis in colon cancer and colon cancer hepatic metastasis has not been elucidated. The aim of this study was to explore the relationship between RBBP4 expression and prognosis of colon cancer patients and to evaluate RBBP4 as a new prognostic marker in these patients. Methods: Eighty colon cancer patients underwent surgical resection of the colon were enrolled. Among them, forty colon cancer patients suffered with hepatic metastasis. The colon cancer tissues, para-colon cancer tissues, and hepatic metastatic cancer tissues were collected from the pathological department for further analysis. The expression of RBBP4 proteins was examined by immunohistochemistry and correlated with clinicopathological parameters. The Cancer Genome Atlas (TCGA) database was used to validate the expression and explore its relationship with clinical characteristics. Results: RBBP4 was up-regulated in the colon cancer tissues compared with the para-colon cancer tissues. The analysis of TCGA database verified the upregulation of RBBP4 in the colon cancer tissues and RBBP4 overexpression was correlated with nerve invasion and poor outcomes of chemotherapy. Moreover, the positive rate of RBBP4 expression in 40 colon cancer patients with hepatic metastasis was higher in the hepatic metastatic cancer tissues (39/40, 97.5%) than in the colon cancer tissues (26/40, 65.0%). Our clinicopathological analysis showed that RBBP4 expression was significantly correlated with vascular invasion, hepatic metastasis, and lymph node involvement (all P < 0.05). Additionally, the survival analysis demonstrated that RBBP4 over-expression was correlated with poor prognosis. Conclusions: RBBP4 was upregulated in the colon cancer. RBBP4 may be a novel predictor for poor prognosis of colon cancer and colon cancer hepatic metastasis.

Retrospective study evaluating association of colorectal tumors and hepatitis C virus

BACKGROUND Chronic hepatitis C virus(HCV)has been associated with hepatic and extrahe-patic malignancies.Limited studies have shown an association between colorectal adenomas and HCV populations.AIM To study the prevalence of colorectal adenomas in patients with HCV compared to the general population and to evaluate if it is an independent risk factor for colorectal adenomas.METHODS Patients were divided into HCV and non-HCV based on their HCV RNA titers.Patients with alcoholic liver disease,hepatitis B infection,and inflammatory bowel disease were excluded.Continuous variables were analyzed using the Mann-Whitney U test,and categorical variables usingχ^(2) with P<0.05 were considered statistically significant.The significant covariates(independent variables)were matched in both groups by propensity score matching,followed by multivariate regression analysis.RESULTS Of the 415 patients screened,109 HCV patients and 97 non-HCV patients with colonoscopy results were included in the study.HCV patients were older,had a smoking history,had less frequent aspirin use,and had a lower body mass index(BMI)(P<0.05).The HCV cohort had a significantly increased number of patients with adenomas(adenoma detection rate of 53.2%vs 34%.P=0.006).We performed a propensity-matched multivariate analysis where HCV infection was significantly associated with colorectal adenoma(OR:2.070,P=0.019).CONCLUSION Our study shows a significantly higher rate of adenomas in HCV patients compared to the general population.Prospective studies would help determine if the increase in adenoma detection lowers the risk for colorectal cancer.

Techniques and feasibility of laparoscopic extended right hemicolectomy with D3 lymphadenectomy

AIM: To illustrate the critical techniques and feasibility of laparoscopic extended right hemicolectomy (LERH), according to our previous experience.

Prognostic significance of red blood cell distribution width in gastrointestinal disorders

The red blood cell distribution width(RDW) is a routinely measured and automatically reported blood parameter,which reflects the degree of anisocytosis. Recently,the baseline RDW was found to have clinical significance for assessing clinical outcome and severity of various pathological conditions including cardiovascular diseases,sepsis,cancers,leukemia,renal dysfunction and respiratory diseases. A myriad of factors,most of which ill-defined,have an impact on the red cell population dynamics(i.e.,production,maturation and turnover). A delay in the red blood cell clearance in pathological conditions represents one of the leading determinants of increased anisocytosis. Further study of RDW may reveal new insight into inflammation mechanisms. In this review,we specifically discuss the current literature about the association of RDW in various disease conditions involving the gastrointestinal and hepatobiliary systems. We also present some of the related measurements for their value in predicting clinical outcomes in such conditions. According to our data,RDW was found to be a valuable prognostic index in gastrointestinal disorders along with additional inflammatory biomarkers(i.e.,C reactive protein,erythrocyte sedimentation rate,and platelet count) and current disease severity indices used in clinical practice.

Could hepatic ablation promote development of colon cancer hepatic metastases?

Introduction Colon cancer is currently the third most common cancer and cause of cancer-related deaths in the United States.Approximately 35–55%of patients with colorectal cancer present with metastatic disease;of these,10–20%of patients have resectable disease,with the liver being the most common site of metastasis(1).

超顺应经内镜钳道结肠支架治疗肝脾曲结肠恶性梗阻7例

目的 评价超顺应经内镜钳道结肠支架治疗肝脾曲结肠恶性梗阻的可行性和治疗效果。方法 2013年9月至2014年7月超顺应经内镜钳道结肠支架治疗肝脾曲结肠恶性梗阻患者7例。内镜及透视引导下行支架置入，评价其技术和近期临床成功率、并发症和临床移位率。结果 恶性结肠梗阻部位肝曲1例，脾曲6例，平均曲度为125.7°±20.7°，技术均获成功，无支架相关性并发症。支架姑息性治疗3例，手术过渡治疗4例，7例临床梗阻均缓解，患者腹围由术前的（87±3） cm降至术后7 d的（70±6） cm。4例行1期手术，支架置入时间为8～10 d，平均（9.3±1.0） d，无吻合口瘘和术后再狭窄。生存期为4～14个月，平均（8.7±3.6）个月。结论 超顺应经内镜钳道结肠支架治疗肝脾曲结肠恶性梗阻安全有效，可作为肝脾曲恶性梗阻的首选治疗方法。

牡蛎提取物抗肿瘤作用的实验研究

以每天0.2ml(20mg)剂量的牡蛎提取物连续10d胃饲荷HAC鼠肝癌的Balb/c小鼠,发现宿主因荷瘤而下降的免疫指标明显回升,包括总T细胞数,T辅助细胞百分比,丝裂原诱发的淋巴细胞转化强度,和NK细胞的杀伤活性。瘤重亦较对照组明显减轻(P<0.01),宿主成活期延长。用相同剂量的牡蛎提取物胃饲长有人结肠癌的裸鼠共15d,发现肿瘤体积明显减少为对照的44.6％,(P<0.01)。结果提示牡蛎提取物可能通过增强宿主免疫功能,特别是其中天然杀伤细胞活性而抑制肿瘤生长。

小鼠结肠癌肝转移模型的建立及其活化肝星状细胞的表达

目的建立小鼠结肠癌肝转移模型,并研究肝星状细胞(hepatic stellete cell,HSC)与结肠癌肝转移的相关性。方法采用囊袋法瘤块盲肠原位移植建立15只小鼠结肠癌肝转移模型,免疫组化法观察活化的HSC在转移灶、癌旁组织及未转移肝组织内的表达情况。结果建模后3周结肠癌肝转移率为40%,4周转移率为60%。转移灶中活化HSC的表达显著高于癌旁组织和未转移肝组织。结论囊袋法瘤块盲肠原位移植是较理想的结肠癌肝转移模型的制作方法;肝脏局部免疫微环境中活化HSC的表达可能参与结肠癌肝转移过程中的免疫调控。

多烯磷脂酰胆碱对奥沙利铂联合氟尿嘧啶所致荷瘤裸鼠肝损伤的保护作用

目的探讨多烯磷脂酰胆碱对奥沙利铂联合氟尿嘧啶所致肝损伤的保护作用。方法 30只BALB/c裸鼠皮下种植结肠癌HCT116细胞制备荷瘤裸鼠模型,随机分为3组:肝损伤组,实验首日腹腔注射奥沙利铂(6 mg·kg^(-1)·d^(-1))0.2 mL,同时连续7 d腹腔注射氟尿嘧啶(20 mg·kg^(-1)·d^(-1));多烯磷脂酰胆碱组,在给予等量氟尿嘧啶和奥沙利铂前30 min,腹腔注射多烯磷脂酰胆碱(85 mg·kg^(-1)·d^(-1))0.2 mL,共7 d;荷瘤空白组,注射生理盐水作为对照。取各组裸鼠肝脏,石蜡切片,HE染色,光学显微镜下观察肝脏组织的变化;制作超薄切片,电子显微镜下观察肝细胞超微结构的变化;制作10%肝组织匀浆,黄嘌呤氧化酶法检测肝组织超氧化物歧化酶(SOD)活性,比色法检测过氧化氢酶(CAT)活性。结果肝损伤组裸鼠肝脏的胞质局部溶解,线粒体膜破损,细胞核膜水肿模糊,肝窦扩张,多烯磷脂酰胆碱部分逆转了这些损伤。与荷瘤空白组相比,肝损伤组SOD和CAT的表达明显降低(P<0.05);与肝损伤组相比,多烯磷脂酰胆碱组SOD和CAT的表达升高(P<0.05)。说明多烯磷脂酰胆碱能减轻化疗药物对肝脏的毒性作用,抑制氧化应激反应。结论多烯磷脂酰胆碱对氟尿嘧啶联合奥沙利铂引起的肝损伤具有预防、保护作用,该作用可能与其膜修复和抗氧化应激反应的作用有关。

肝纤维化对结肠癌肝转移的影响及TIMP-1、CTGF在其过程中的机制研究

目的:通过建立小鼠肝纤维化模型及肝纤维化基础上的结肠癌肝转移模型,阐明肝纤维化对肝转移癌发生的影响,探讨TIMP-1、CTGF在肝纤维化抑制结肠癌肝转移中的作用。方法:BALB/c小鼠76只,随机分为A、B两组,A组为正常对照组,B组采用CCl4灌胃法构建肝纤维化模型。病理切片证实肝纤维化模型制作成功后,将B组随机分为B1和B2两组,A组同时随机分为A1和A2两组,每组均为19只。取A2和B2组,将培养好的小鼠结肠癌CT26细胞应用脾脏种植切除脾脏法构建结肠癌肝转移模型。2周后处死各组动物,比较A2和B2组小鼠肝转移率,并采用免疫组化方法对TIMP-1、CTGF在各组肝脏中的表达进行分析。结果:动物模型构建成功,病理切片证实肝纤维化及肝转移癌的发生。A2组肝转移发生率为82.4%(14/17),B2组肝转移发生率为25%(4/16),差异有统计学意义(P<0.05)。TIMP-1、CTGF在B1、B2组肝脏的表达与A1、A2组相比均升高,差异有统计学意义(P<0.05)。结论:肝纤维化对肝转移癌的发生有抑制作用。TIMP-1、CTGF可能在肝纤维化抑制结肠癌肝转移中发挥作用。

DR-70^(TM)检测在消化系统肿瘤中的应用

目的评价 DR- 70 TM在消化系肿瘤筛查中的价值。方法应用 EL ISA对 135例确诊为食道癌、胃癌、肠癌或肝癌的患者和 16 6例年龄相当的健康者进行了对照检测。结果以 5 .3mg/ L 为临界值 ,食道癌阳性率为92 .9%,胃癌阳性率为 92 .9%,肠癌阳性率为 83.3%,肝癌阳性率为 83.8%,合计总阳性率为 85 .8%;与健康对照组结果比较 ,P<0 .0 0 1,差异呈高度显著性。结论 DR- 70

BALB/c与SCID裸小鼠高侵袭性人结肠癌肝转移模型的比较研究

目的建立裸小鼠人结肠癌肝转移的高侵袭性模型,比较BALB/c鼠与SCID鼠的人结肠癌肝转移模型,为侵袭性人结肠癌的研究寻找可靠的动物模型。方法首先将人结肠癌细胞株HT-29细胞悬液接种于免疫功能正常BALB/c鼠的脾包膜下,然后将其肝转移肿瘤组织通过原位移植方式分别种植于免疫缺陷BALB/c鼠和SCID鼠的盲肠浆膜下,而第三组直接将HT-29种植于结肠,最后观察三组的成瘤及死亡情况,以及淋巴转移率、肝转移率、肺转移率及腹腔种植率等。结果术后21 d观察,40只BALB/c鼠有38只成瘤,其余2只死亡;40只SCID鼠有33只成瘤,其余7只死亡;第三组40只(20只BALB/c鼠/20只SCID鼠)裸小鼠虽有29只成瘤,且仅1只死亡,但肝转移率(24.1%)较低,不适于建立高侵袭模型。前两组在原位移植瘤大小、转移和种植率上差异无统计学意义(P>0.05),而两组成瘤率和死亡率的差异有统计学意义(P<0.05)。结论将筛选出的人结肠癌肝转移组织用于建立模型,能有效模拟高侵袭性等生物学特性,再结合BALB/c鼠价格较低的优势,所以更适宜作为人结肠癌肝转移的可靠动物模型。

乙肝病毒感染状态及表面抗原/抗体水平与结肠癌分期和预后的关联

目的观察结肠癌患者乙肝病毒感染状态及表面抗原/抗体水平,分析其与结肠癌分期的关联,从而间接评估结肠癌患者合并乙型肝炎对其预后的影响。方法收集福建省立医院收治的85例结肠癌患者,采用SPSS16.0统计软件回顾性分析乙肝病毒感染状态对结肠癌浸润深度、区域淋巴结转移和远处转移的影响。结果乙肝病毒感染状态对结肠癌原发灶浸润深度(T)(P=0.331)和结肠癌区域淋巴结转移(N)的影响差异无统计学意义(P=0.098)。合并乙肝病毒阳性的结肠癌患者其区域淋巴结转移度明显低于乙肝病毒阴性的亚组(8.1%vs.17.8%),且无区域淋巴结转移的结肠癌患者血清中Hbs Ab水平较发生淋巴结转移的亚组患者明显升高(240.111 m IU/ml vs.178.161 m IU/ml)。乙肝病毒感染状态对结肠癌患者发生远处转移(M)以及肝转移的影响差异均具有统计学意义(均P<0.001)。不论是乙肝病毒感染还是乙肝疫苗相关的乙肝病毒阳性患者,肝转移发生率均显著低于乙肝病毒阴性的患者(P=0.039,P<0.001)。结论结肠癌合并乙肝病毒表面抗体水平高表达对区域淋巴结转移可能具有潜在的抑制作用。乙肝病毒阳性对结肠癌发生远处转移(尤其对肝转移)呈显著性负相关。乙肝病毒感染状态以及表面抗原/抗体水平显著性影响结肠癌患者的分期及预后。

HOXB7基因敲减对裸鼠结肠癌肝转移模型的抑癌机制研究

目的研究HOXB7基因敲减对裸鼠结肠癌肝转移模型的抑癌机制。方法将转染pcDNA3.1-HOXB7敲减或pcDNA3.1-scramble重组质粒的人结肠癌细胞株HT29经裸鼠脾脏接种建立稳定的肝转移模型。参与模型的实验裸鼠共20只,其中10只HOXB7基因敲减鼠列为研究组,10只scramble鼠列为对照组。制模4周后解剖观察两组裸鼠模型肝转移瘤的组织形态学和组织病理学变化。结果裸鼠结肠癌肝转移模型的成瘤率为100%(20/20)。组织形态学角度分析:与对照组比较,研究组显著抑制裸鼠模型的肝转移瘤形成;递减或衰减肝转移瘤的大小、肝体质量、病灶间融合、肝表面隆凸及肝转移评分,差异有统计学意义(P<0.05)。组织病理学角度分析:与对照组比较,研究组肿瘤细胞排列稀疏、边缘型分布、浸润深度浅、中央区坏死或凋亡成片,差异有统计学意义(P<0.05)。结论HOXB7基因敲减可有效抑制裸鼠模型的结肠癌肝转移瘤形成,至于具体的抑癌模式和量化标准的制定需有待于进一步考证。

肝动脉介入联合靶向治疗结肠癌肝转移临床研究

目的:评价肝动脉介入联合靶向治疗结肠癌肝转移的疗效及药物不良反应。方法:78例结肠癌肝转移患者随机分为干预组和对照组,干预组(42例)应用肝动脉介入((TACE))联合靶向治疗方案治疗,对照组(36例)单纯采用肝动脉介入治疗(TACE)方案治疗。结果:干预组和对照组的近期有效率分别为80.9%和55.6%,差异有显著性意义(P﹤0.05)。治疗后0.5、1、2、3、5年生存率,干预组为94.3%,68.8%,33.7%,18.4%,10.3%,对照组为84.2%,54.6%,19.6%,8.1%,2.5%,两组之间差异有显著性意义(P﹤0.05)。在药物不良反应及并发症方面两组之间无显著性差异。结论:应用肝动脉介入联合靶向治疗结肠癌肝转移,优于单纯肝动脉介入治疗的效果。

20例结直肠癌肝转移同期切除并发症的护理

目的探讨结直肠癌肝转移同期切除患者的护理方法。方法回顾性分析20例同期切除结直肠癌肝转移患者的临床资料及术后并发症护理方法,重点介绍并发症的临床观察及护理。结果20例结直肠癌肝转移患者出现Clavien-Dindo分级Ⅲ级以上并发症仅3例,患者术后恢复良好,无围术期死亡。结论加强对结直肠肝癌转移同期切除并发症的临床观察和护理,有利于预防和减少并发症的发生,提高手术治疗效果,改善患者生活质量。

肝动脉灌注化疗栓塞与全身静脉化疗治疗结肠癌肝转移疗效比较

目的比较经肝动脉灌注化疗栓塞与全身静脉化疗治疗结肠癌肝转移的疗效,旨在为临床制定合理治疗方案提供依据。方法回顾性分析60例临床分期相同的结肠癌肝转移患者资料,按化疗方法将其分为肝动脉灌注化疗栓塞组及全身静脉化疗组,每组30例。两组均采用FOLFOX方案化疗,治疗前后行CT检查、血常规、肝肾功能。分析比较两组的临床有效率,临床受益率,1、2、3年生存率以及中位生存期。结果肝动脉化疗栓塞组的临床有效率和临床受益率(66.66%、83.33%)显著高于全身静脉化疗组(43.33%、60.00%)(P<0.05),不良反应发生率(40.00%)显著低于全身静脉化疗组(60.00%)(P<0.05),且1、2、3年生存率和中位生存期均高于全身静脉化疗组(87.5%VS 67.7%,66.7%VS 41.5%,55.4%VS 20.1%,27.7 VS 19.1个月,P均<0.05)。结论肝动脉灌注化疗栓塞治疗结肠癌肝转移临床有效率和临床受益率高,不良反应率低,生存率高,中位生存期长,较全身静脉化疗显示出更明显的优势。